Hepatocellular carcinoma - Pathogenesis

The tumor is usually white, sometimes stained with bile and may contain foci of hemorrhage and necrosis. Large intrahepatic branches of the portal and hepatic veins are often thrombosed and contain tumor masses. There are 3 forms of hepatocellular carcinoma: expansive (or nodular - in the form of large nodes with clear boundaries), massive (or infiltrative) and multifocal (or diffuse). In the nodular form of hepatocellular carcinoma, it most often develops in the liver not affected by cirrhosis; in Japan, encapsulated tumors are observed. In the West and in African countries, hepatocellular carcinoma is represented in most cases by massive and diffuse forms.

Hepatocellular carcinoma

The cells resemble normal hepatocytes and are arranged in compact finger-like processes or solid trabeculae. The tumor resembles normal liver tissue to varying degrees. Tumor cells sometimes secrete bile and contain glycogen. There is no intercellular stroma, and tumor cells line blood-filled spaces.

Tumor cells are usually smaller than normal hepatocytes; they are polygonal in shape and have granular cytoplasm. Atypical giant cells are sometimes found. The cytoplasm is usually eosinophilic, becoming basophilic with increasing grade of malignancy. The nuclei are hyperchromatic and vary in size. Predominantly eosinophilic tumors are sometimes encountered. Necrotic foci are often noted in the center of the tumor. An early sign is infiltration of the periportal lymphatics by tumor cells. In approximately 15% of patients, usually with high serum alpha-FP concentrations, PAS-positive diastase-resistant globular inclusions are found, which may represent glycoproteins produced by hepatocytes.

_{Alpha 1-} antitrypsin and a-fetoprotein are also often detected in the tumor.

In terms of malignancy, liver tumors can correspond to the entire range - from benign regeneration nodes to malignant tumors. Dysplasia of hepatocytes occupies an intermediate position. The probability of malignancy is especially high in the presence of small dysplastic hepatocytes. An increase in the density of tumor cell nuclei by 1.3 times or more compared to the density of normal hepatocyte nuclei indicates highly differentiated hepatocellular carcinoma.

Electron microscopy data. The cytoplasm of human hepatocellular carcinoma cells contains hyaline. Cytoplasmic inclusions include filamentous bodies and autophagic vacuoles.

Clear cell hepatocellular carcinoma

Tumor cells in this form of hepatocellular carcinoma have nonstaining, often foamy cytoplasm. Lipids and sometimes glycogen are found in the large cytoplasm. The tumor is often accompanied by hypoglycemia and hypercholesterolemia; the prognosis may vary.

Hepatocellular carcinoma with giant cells

In this rare form of hepatocellular carcinoma, some areas of the tumor contain clusters of giant cells resembling osteoclasts surrounded by mononuclear cells. In other areas, the tumor has a typical histologic picture for hepatocellular carcinoma.

Tumor spread

Intrahepatic. Metastases may affect the entire liver or be limited to one lobe. Metastasis usually occurs hematogenously, since tumor cells are adjacent to vascular spaces. Lymphatic metastasis and direct growth into healthy tissue are also possible.

Extrahepatic. The tumor can grow into small and large branches of the portal and hepatic veins, as well as into the vena cava. Metastases of hepatocellular carcinoma can also be found in esophageal varices, even if they are sclerosed. This is the route by which metastasis to the lungs can occur. These metastases are usually small in size. Tumor emboli can lead to thrombosis of the pulmonary arteries. Systemic spread can lead to metastases in any part of the body, especially in the bones. Regional lymph nodes in the porta hepatis, as well as the lymph node chains of the mediastinum and neck, are often affected.

Tumor involvement of the peritoneum leads to hemorrhagic ascites. This complication may be a sign of the terminal stage of the disease.

Histological signs of metastases. Metastases resemble the primary tumor in structure, and even signs of bile formation may be detected. However, sometimes the cells of the primary tumor and metastases may differ significantly. The presence of bile or glycogen in the cells of metastases indicates that the primary tumor is of hepatic origin.

[ 1 ], [ 2 ], [ 3 ], [ 4 ], [ 5 ], [ 6 ], [ 7 ], [ 8 ], [ 9 ], [ 10 ], [ 11 ]